目的:生物治疗(BTs)对于治疗小儿炎症性肠病(PIBDs)至关重要。肝酶升高有时会导致BT成功,然而,阐明研究很少。我们在引入BT后讨论了肝脏生物化学,并搜索了它们的决定因素。
方法:我们确定了接受英夫利昔单抗治疗的PIBD患者,阿达木单抗,维多珠单抗,或者是儿童医院的ustekinumab,赫尔辛基大学,芬兰,在2000-2023年,并跟踪他们的丙氨酸转氨酶(ALT)和γ-谷氨酰转肽酶(GT)水平24个月。ALT根据年龄和性别特异性的正常上限进行分类。我们忽略了46例原发性硬化性胆管炎伴/不伴自身免疫性肝炎(AIH)的患者,预处理AIH诊断,从分析开始BT时肝脏酶升高。
结果:在403例患者的618次BT发作中,22.2%显示ALT或GT增加(ALT117,GT4,ALT/GT16次)。所有ALT升高(n=133),41.4%发生在前3个月内。ALT升高在英夫利昔单抗(占BTs的59.5%)后比其他BTs更常见(25.9%vs.14.2%,调整后的比值比[OR]:2.41,95%置信区间[CI]:1.23-4.72)。AIH跟随1.5%(n=9)的BT发作。95%的ALT升高在6个月内解决。一般情况下,抗生素暴露(特别是甲硝唑)与ALT升高(调整后的OR:5.76,95%CI:2.40-13.9)和开始BT前的疾病持续时间短相关,ALT明显升高(调整后的OR:1.10,95%CI:1.01-1.22)。
结论:在开始BT(尤其是英夫利昔单抗)后3个月内,良性ALT升高是常见的,并且几乎不导致停止治疗。AIH是BT第一年的罕见发现。
OBJECTIVE: Biological treatments (BTs) are essential in managing pediatric inflammatory bowel diseases (PIBDs). Elevated liver enzymes sometimes succeed BT, yet elucidating studies are scarce. We addressed liver biochemistry after introducing BT and searched for their determinants.
METHODS: We identified PIBD patients receiving
infliximab, adalimumab, vedolizumab, or ustekinumab at the Children\'s Hospital, University of Helsinki, Finland, in 2000-2023, and followed their alanine transaminase (ALT) and γ-glutamyl transpeptidase (GT) levels for 24 months. ALT was categorized based on the age- and sex-specific upper limit of normal. We disregarded 46 patients with underlying primary sclerosing cholangitis with/without autoimmune hepatitis (AIH), pretreatment AIH diagnosis, and elevated liver enzymes at the beginning of BT from the analyses.
RESULTS: Of 618 BT episodes in 403 patients, 22.2% exhibited increased ALT or GT (ALT in 117, GT in 4, and both ALT/GT in 16 episodes). Of all ALT elevations (n = 133), 41.4% occurred within the first 3 months. ALT elevation was more common after
infliximab (representing 59.5% of BTs) than other BTs (25.9% vs. 14.2%, adjusted odds ratio [OR]: 2.41, 95% confidence interval [CI]: 1.23-4.72). AIH followed 1.5% (n = 9) of BT episodes. Ninety-five percent of ALT elevations resolved within 6 months. Antibiotic exposure (particularly to metronidazole) was associated with ALT elevation in general (adjusted OR: 5.76, 95% CI: 2.40-13.9) and short disease duration before starting BT with notable ALT elevation (adjusted OR: 1.10, 95% CI: 1.01-1.22).
CONCLUSIONS: Benign ALT elevation is common within 3 months after starting BT (especially
infliximab) and scarcely led to cessation of the treatment. AIH is a rare finding during the first year of BT.